The NLRP3 Inflammasome Mediates in vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA

By I. C. Allen, Margaret A. Scull, C. Moore, E. Holl, Erin Mcelvania-Tekippe, D. Taxman, E. Guthrie, R. Pickles, J. Ting. Immunity, 2009

1,157 citations recorded by the source corpus.

SUMMARY NLR genes mediate host immunity to various pathogenic stimuli. However, in vivo evidence for NLR involvement in viral sensing has not been widely investigated and remains controversial. As an ultimate test of the physiologic role of NLRP3 during RNA viral infection, this work explores the in vivo role of NLRP3 inflammasome components during influenza virus infection. Mice lacking Nlrp3, ASC, or Caspase-1, but not Nlrc4, exhibit dramatically increased mortality but reduced immune response following influenza virus exposure. Utilizing analogs of dsRNA (poly(I:C)) and ssRNA (ssRNA40), we demonstrate that NLRP3-mediated response can be activated by RNA species. Mechanistically, NLRP3 inflammasome activation by influenza virus is dependent upon lysosomal maturation and reactive oxygen species. Inhibition of ROS induction eliminated IL-1β production in animals during influenza infection. Together, these data place the NLRP3 inflammasome as an essential component in host defense against influenza infection through the sensing of viral RNA.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1250f11c30671b35e4bc7f1b7e84ff4622024391

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Citations in the corpus

Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, neutral): “rectly recognizing viral RNA is scant [31], however, NLRs are more possibly involved in detecting intracellular homeostasis perturbations or danger signals, such as ROS production [32,33].”
The Airway Epithelium: Soldier in the Fight against Respiratory Viruses (2011, background): “While NOD1 and NOD2, the first NLRs identified, are involved mainly in the recognition of bacterial peptidoglycans, NLRP3 seems to be important for the immune response to respiratory viruses (5, 118, 192, 280).”
Biology and pathogenesis of chikungunya virus (2010, background): “There has been a surge of new information regarding the role of the inflammasome , which is well recognized as being crucial for IL-1β production following bacterial infection and also seems to participate in the control of viruse”
Microbiota regulates immune defense against respiratory tract influenza A virus infection (2011, background): “Two other groups, using high lethal doses of influenza virus challenge, demonstrated that in the absence of the NLRP3 inflammasome, mice succumb to high doses of A/PR8 infection due to innate immune defects (4, 5).”
The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases (2011, background): “NLRP3 also interacts with CARD8 (also known as CARDINAL and TUCAN), but the role of CARD8 is not currently understood because its elimination in a human monocytic cell line has not altered inflammasome function (15).”
Inflammasomes and their roles in health and disease. (2012, background): “…2009, Joly et al. 2009, Said-Sadier et al. 2010); viral pathogens such as influenza A, encephalomyocarditis virus, and vesicular stomatitis virus (Allen et al. 2009, Ichinohe et al. 2010, Rajan et al. 2011, Thomas et al. 2009); and the parasites Schistosoma mansoni and Dermatophagoides…”